Regulation of Neurosteroid Biosynthesis

The brain is not only a site for ovarian steroid metabolism; it is also a site of sex steroid biosynthesis.  We have determined that estradiol from developing ovarian follicles stimulates the synthesis of progesterone in the hypothalamus, and this neuroprogesterone is necessary for the initiation of the LH surge.  Indeed, blocking steroidogenesis in the hypothalamus of gonadally intact rats prevents the LH surge and ovulation.   Males and aging females, neither of which exhibit estrogen positive feedback also lack the ability to increase progesterone synthesis in the hypothalamus. The estradiol-induced hypothalamic progesterone synthesis occurs in astrocytes.  These cells express membrane ERα receptors that transactivate metabotropic glutamate receptor stimulating the release of intracellular calcium stores and augmenting progesterone synthesis.